POS0358 JAK2 MUTATION, TNF-Α AND IL 6 PREDICT RESPONSE TO JAK INHIBITOR IN RHEUMATOID ARTHRITIS PATIENTS
Authors: Y. Adel Abdelsalam Hussein, Y. Sadeq
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> STAT4 is activated by the JAK family members Tyk2 and JAK2 in response to IL and TNF, with subsequent down-stream signaling to promote Th1 mediated autoimmunity [1]. JAK inhibitors [2] are type of medication that function by inhibiting activity of one or more of the Janus kinase family of enzymes. These inhibitors have therapeutic application in the treatment of cancer and inflammatory diseases such as rheumatoid arthritis [3]. <h3>Objectives</h3> Study impact of JAK2 mutation, TNF-α and IL 6 levels on response to JAK inhibitors and ACR response criteria. <h3>Methods</h3> The study included 120 newly diagnosed rheumatoid arthritis patients and 80 matched controls. All patients started therapy with csDMARDs. 70 patients failed to achieve adequate response so, they were shifted to Baricitinib. JAK2 mutation assessed by PCR in blood samples, TNF-α and IL 6 were measured by ELISA in serum of patients at diagnosis, before and after Baricitinib treatment. <h3>Results</h3> 102 females (85%) and 18 males (15%) with age mean ± SD (years); (47.7±7.5). Pretreatment JAK2 mutation, TNF-α and IL 6 were significantly high in patients than control. JAK2 mutation were more presented in young age patients (mean ± SD; 47.1 ±3.2 vs 51.4 ± 7.9 in mutant vs non-mutant JAK2 patients, respectively with <i>P</i> 0.03). Mutant JAK2 was significantly linked to severity of disease by DAS28; 70% of patients with DAS28 (≤ 2.6) were non-mutant JAK2 vs 30% patients mutant JAK2 while 73.1% of patients with DAS28 (&gt; 5.1) were mutant JAK2 vs 26.9% patients non-mutant JAK2 (P 0.04). 70 patients were csDMARD incomplete responders. Jak2 mutation was significantly presented in these group comparing to patients achieved response to csDMARDs (P 0.002) associated with significant high serum TNF-α (P 0.03) and IL 6 (P 0.001). These refractory patients allowed to receive Baricitinib (single or with other antirheumatic). ACR20 response criteria was significantly better in patients with JAK2 mutation compared with those non mutant after Baricitinib therapy at week 12 (65 versus 31 percent, P 0.04). Also, Baricitinib responders were significantly have high serum TNF-α (P 0.002) and marginal significance high serum IL 6 (P 0.06). <h3>Conclusion</h3> JAK2 mutation in RA patients associated with high disease activity score and inadequate response to csDMARDs. Pretreatment detection of JAK2 mutation in RA patients with high serum level of TNF-α and IL 6 predict a good response to JAK inhibitors with better ACR response criteria. <h3>References</h3> [1]Watford, W.T., et al., <i>Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4.</i> Immunol Rev, 2004. <b>202</b>: p. 139-56. [2]Kontzias, A., et al., <i>Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease.</i> Curr Opin Pharmacol, 2012. <b>12</b>(4): p. 464-70. [3]Norman, P., <i>Selective JAK inhibitors in development for rheumatoid arthritis.</i> Expert Opin Investig Drugs, 2014. <b>23</b>(8): p. 1067-77. JAK2 mutation and ACR20 after <b>Baricitinib treatment.</b> <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.